ECHELON-1 Trial: Significance in Hodgkin Lymphoma

Stephen M. Ansell, MD, PhD: Hodgkin lymphoma is a disease where we have made a lot of progress over recent years, but we’d clearly like to keep moving forward. In Hodgkin lymphoma, one of the challenges is in this space of managing advanced staged patients, patients with stage 4 and stage 3 disease. Those are patients where there is still an unmet need, and we need to build on ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy. ABVD, which is a 4-drug combination, is really a standard approach for patients with advanced Hodgkin lymphoma.

The ECHELON-1 trial is a comparison of a new combination, AVD (doxorubicin, vinblastine, and dacarbazine) chemotherapy, with the addition of a further agent, brentuximab vedotin. Brentuximab vedotin is an antibody-drug conjugate. It has an antibody which binds to the tumor cell, but also delivers a toxin which kills the cells. The phase 1 trial combining that agent with AVD chemotherapy showed a very high response rate. So, there is a lot of excitement about using that combination. And so, the ECHELON-1 trial was a large international multi-institutional study where a comparison was made between ABVD, the standard, and AVD chemotherapy plus brentuximab vedotin.

These results were just reported. It was a positive study. It met its primary endpoint. The primary endpoint was the modified progression-free survival. It was 77% in the standard arm and 82% in the experimental arm. One of the exciting parts of the study is that a further analysis, which will be forthcoming, is trying to identify patients who benefit the most. Those might be patients with stage 4 disease, possibly elderly patients. We may see that this potentially more expensive combination will have the greatest impact and be best for patients.

Brentuximab vedotin is an agent that has approval for patients with Hodgkin lymphoma. It’s an antibody-drug conjugate where the antibody delivers the toxin to the tumor cell. In patients who had failed autologous stem cell transplantation, this, in the pivotal trial, showed very good results: a high overall response rate and a complete response rate where it has been very durable. There are patients out beyond 5 years with ongoing benefit. So, that’s now been moved earlier into the course of treatment. It’s being tested as a part of a salvage regimen, and has now been moved into the frontline setting in combination with chemotherapy. So, this is an example of a new drug which has moved from its established place, posttransplant in the third-line setting, to a frontline combination approach.

The FDA has actually given the combination of chemotherapy plus brentuximab vedotin breakthrough status. Because the primary endpoint of the study was met, I would anticipate that this will be an approved indication, now, in the frontline setting for patients with Hodgkin lymphoma. In the near future, I think that this will be an established combination, which will be used for patients with advanced stage Hodgkin lymphoma.

Transcript Edited for Clarity

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Stephen M. Ansell, MD, PhD: Hodgkin lymphoma is a disease where we have made a lot of progress over recent years, but we’d clearly like to keep moving forward. In Hodgkin lymphoma, one of the challenges is in this space of managing advanced staged patients, patients with stage 4 and stage 3 disease. Those are patients where there is still an unmet need, and we need to build on ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy. ABVD, which is a 4-drug combination, is really a standard approach for patients with advanced Hodgkin lymphoma.

The ECHELON-1 trial is a comparison of a new combination, AVD (doxorubicin, vinblastine, and dacarbazine) chemotherapy, with the addition of a further agent, brentuximab vedotin. Brentuximab vedotin is an antibody-drug conjugate. It has an antibody which binds to the tumor cell, but also delivers a toxin which kills the cells. The phase 1 trial combining that agent with AVD chemotherapy showed a very high response rate. So, there is a lot of excitement about using that combination. And so, the ECHELON-1 trial was a large international multi-institutional study where a comparison was made between ABVD, the standard, and AVD chemotherapy plus brentuximab vedotin.

These results were just reported. It was a positive study. It met its primary endpoint. The primary endpoint was the modified progression-free survival. It was 77% in the standard arm and 82% in the experimental arm. One of the exciting parts of the study is that a further analysis, which will be forthcoming, is trying to identify patients who benefit the most. Those might be patients with stage 4 disease, possibly elderly patients. We may see that this potentially more expensive combination will have the greatest impact and be best for patients.

Brentuximab vedotin is an agent that has approval for patients with Hodgkin lymphoma. It’s an antibody-drug conjugate where the antibody delivers the toxin to the tumor cell. In patients who had failed autologous stem cell transplantation, this, in the pivotal trial, showed very good results: a high overall response rate and a complete response rate where it has been very durable. There are patients out beyond 5 years with ongoing benefit. So, that’s now been moved earlier into the course of treatment. It’s being tested as a part of a salvage regimen, and has now been moved into the frontline setting in combination with chemotherapy. So, this is an example of a new drug which has moved from its established place, posttransplant in the third-line setting, to a frontline combination approach.

The FDA has actually given the combination of chemotherapy plus brentuximab vedotin breakthrough status. Because the primary endpoint of the study was met, I would anticipate that this will be an approved indication, now, in the frontline setting for patients with Hodgkin lymphoma. In the near future, I think that this will be an established combination, which will be used for patients with advanced stage Hodgkin lymphoma.